Chitosan derivative, method of making the same and cosmetic composition containing the same

ABSTRACT

Chitosan derivatives formed by acylation of chitosan with a saturated or unsaturated organic diacid anhydride are employed as a skin moisturizing agent in a cosmetic composition comprising an aqueous solution containing 0.1-20 percent by weight of said chitosan derivative.

11111111661 Mates atent Vanierbergbe et a1.

1 1 Apr. 22 1975 CHHTQSAN DERWATHVE, METHOD 01F MAMHNG THIE SAME ANDCQSMETHC COMPOSHTIION CONTAIINHNG THE SAME 1nventors: Guy Vanierberghe,

Montjay-1aTour; Henri Sebag, Paris, both of France Assignee: SocieteAnonyme dite: LOreaL Paris, France Filed: May 8, 1972 App1. No: 251,263

Foreign Application Priority Data May 10. 1971 Luxembourg 63142 Apr. 18.1972 Luxembourg 65186 US. Cl 260/2111 1R; 252/89; 252/352;

lint. C1. C07c 95/04 lFie11d 01 Search 260/21 1 R PrimaryExaminer-Johnnie R. Brown Attorney, Agent. or Firm-Cushman, Darby &Cushman [57] ABSTRACT Chitosan derivatives formed by acy1ation ofchitosan with a saturated or unsaturated organic diacid anhydride areemployed as a skin moisturizing agent in a cosmetic compositioncomprising an aqueous solution containing 01-20 percent by weight ofsaid chitosan derivative.

16 C1aiims, No Drawings CHlITOSAN DEIRHVATHVE, METHOD OF MATKIRNG Til-HESAME AND COSMETIC COMPOSITION CONTAllNllNG THE SAME The presentinvention relates to novel macromolecular compounds derived fromchitosan which present particularly advantageous properties asfilmogens. as sequestrants of ions of heavy metals such as iron andcopper and as skin moisturizing agent for incorporation into cosmeticcompositions.

Chitosan is a product of the deacetylation of chitin, a naturalpolyglucosamine whose amine groups are acetylated and which is found incertain mushrooms and the shells of crustacea.

Since deactylation of chitin by alkaline reagents cannot be performedcompletely, chitosan, which serves as the starting product for compoundsof the invention, comprises in its molecule both free amine residues andacetylamine residues. The degree of deacetylation of chitin is evaluatedby determining by titration the percentage of free base of the molecule,which is generally located below 95 percent.

Chitosan is, by the presence of these free amine groups, a cationicpolymer, which presents the major drawback of being insoluble in analkaline medium.

Known derivatives of chitosan, obtained by alkylation of this compound,hardly differ from chitosan itself as far as their alkaline solubilityis concerned.

To improve this property of chitosan, the applicants have tried to makeits molecule undergo other modifications. The difficulties encounteredin these attempts are explained principally by the fact that chitosan isso]- uble only in an acid medium, in the form of salts. Further, it isknown that it is generally very difficult to achieve condensation oraddition reactions on amine salts. The applicants have now developed aprocess which makes it possible to acylate chitosan. Thus, the presentinvention relates to chitosan derivatives obtained by the acylation ofthis compound by means of saturated or unsaturated organic diacidanhydrides, followed if desired in the case of unsaturated anhydrides,by the addition on the double bonds or compounds with primary orsecondary amine groups to provide other functional substituents.

The novel compounds according to the invention are polymers havingmonomer patterns of the formula 4 (o) CH is R2 i wherein R is selectedfrom the group consisting of hydrogen and methyl and n is equal to (a)O, in which case R R and R, each independently represent a memberselected from the group consisting of hydrogen; methyl; hydroxyl;acetoxy; amino; monoalkylamino wherein the alkyl moiety has 1 to 12carbon atoms or dialkylamino wherein the alkyl moiety has 1 to 3 carbonatoms, said monoalkylamino and dialkylamino being optionally substitutedby one or more amine, hydroxyl, mercapto, carboxyl, alkylthio whereinthe alkyl moiety has 1 to 8 carbon atoms or sulfonic groups; alkylthiowherein the alkyl moiety has 1 to 4 carbon atoms and carries an amineresidue; and a residue of an oligopeptide such as glutathion or aproduct of protein hydrolysis, one at least of radicals R R and R, beinga hydrogen atom and radicals R and R being able, in addition, to formtogether a methylene radical; and to (b) l, in which case R R and R,each represent hydrogen.

The acid and base groups which appear in the mole cules of the polymersaccording to the invention are able to be ionized in an aqueoussolution, thus yielding salts either between two patterns B and C, or inthe same pattern C.

These same ionized forms also appear in the presence of inorganic ororganic bases and acids. The salts formed with these acids or bases are,of course, also a part of the invention.

These salts can be obtained with acids such as, for example,hydrochloric, phosphoric, acetic, lactic, tartaric or citric acid oralternatively with bases such as sodium 3 4 hydroxide, potassiumhydroxide, ammonia, lime, magcan be, for example, maleic anhydride,itaconic anhynesia, alkanolamines such as triethanolamine, triiso drider C t aCCmiC anhydride. propanolamine, aminomethylpropanol, or ami Inthe case where the starting anhydride is unsatuthyl rop nedi l, or witha i id d more i rated, this acylation reaction can be followed by anadlarly amino a ids of a ba nat h as l i or 5 dition reaction whichmakes it possible to achieve a g i range of quite varied products.

The com ound ordi g t th invention are The addition reactions accordingto the invention pared, according to a process developed by the applicanfor the most P be Performed at 3 P above 7 and cants, by acylating thechitosan by means of a saturated at a temperature between 20 and forSeveral or t t d h d id f h f l 10 hours. Advantageously the reaction iscarried out in a 3 R u R -C=C-H or R' -JJ- 0 -C- 1 L 2 Y n l H C 0 O COwherein R has the meaning given above and wherein nitrogen atmosphere.

when n is equal to O, R' R; and R each indepen- The amino reagents, usedin these reactions, are presdently represent hydrogen, methyl or acetoxywith the ent in a proportion of 0.1 to 10 moles per unsaturated provisothat at least one of these radicals is hydrogen pattern, this proportionbeing a function of the properand radicals R' and R';, can further formtogether a ties desired. Thus, for example, in the case ofpolyfuncmethylene residue; and wherein when n is equal to 1, tionalreagents it is possible to obtain, as a function of R' R and R. eachrepresent hydrogen, after which, this number of moles, mobile, clearsolutions, gels or in the case where an unsaturated anhydride is used,the unds that are no longer soluble in water because product obtainedcan be subjected to an addition reacf too great a reticulation.

tion with at least a prim y n ry amine: Whose The reagents used in theaddition reactions according hydrocarbon residue can be interrupted byone or more t h invention can be ammonia; monoor polyamines nitrogenatoms and/0r substituted by one or more such as methylamine, ethylamine,propylamine, butylaamine, .hydroxyl, carboxyl, sulfonic or mercaptoresimine, hexylamine, octylamine, dimethylamine, diethylduesamine,ethylenediamine, hexamethylenediamine, di-

The chitosan acylation reaction is performed by addethylehetriamlhertl'icthylehstetramlhe and ing to an aqueous solution of a chitosan salt,having a thylehepehtamme; alkaholamlhes such as mohoethaconcentration ofl to 20 weight percent thereof, alterholamihe, isopropaholamlhe anddiethaholamihe; nately and by fractions, on the one hand, a base dilutedCaptO-amihes such as p ethylamihel amines solution intended to releaseamine functions of the chiw acid functions such as glycocoh, alaninelehcihe 052m and to Salify the i f d and on the other 40 isoleucine,valine, aspartic acid, glutamic acid, serine,

hand, the anhydride defined above. The reaction is perlysine,cysteiheimethiohihe cysteic PehiChlamihe, formed between 10 and 50C andpreferably between and mffthyhaurlhei f f f hlore complex compohhds 15and 30C, by using 0.3 to 2 moles Ora saturated ancomprlsmg yp p lmkmgsas glutathwn and p hydride per equivalent of amine present in thechitotelhhydrolyzateswhen a mercapto-amine is used the San, or 1 to 2moles f unsaturated anhydride addition on the double bond can also bemade by the amine group or mercapto group.

For the preparation of the compounds according to the invention, it isdesirable to use chitosan comprising from 70 to 95 percent of free aminegroups. The percentage of these amine groups can be determined, in aknown way, by dissolving of a sample in a known and excessive amount ofhydrochloric acid which is determined back by a soda solution.

The chitosan that can be used for the purpose of the invention can alsobe selected as a function of the viscosity of their solutions. Theviscosity of their solutions at 2 percent in 3 percent acetic acid,measured at 25C after 24 hour can vary from 3 to 130 centipoises.

equivalent of amine present in the chitosan. The anhydride can be usedin this reaction either in powder form or in the form of a solution inan inert solvent such as, for example, dioxane, tetrahydrofuran or ethylacetate.

Since the addition of the base causes partial precipitation of thechitosan, this reaction is performed in a heterogeneous medium. Further,since the anhydrides are unstable compounds in water, they can hydrolyzeinto the corresponding diacids, giving rise to a secondary reaction.However, despite these unfavorable conditions, the rate of acylation,computed from the acid number corresponding to this secondary reaction,is

generally greater than 70 percent All the compounds obtained accordingto the process The chitosan salts used in this alkylation reaction are,0 of the invention can he precipitated from their aqueous for example,the hydrochloride or acetate, while the solution by modification of thepH and/Or by addition bases can be sodilfm or Potassium hydroxldei h ofa solvent such as alcohol or acetone. Further, they and preferably, acidor neutral carbonates of sodium or can be isolated by other processessuch as dialysis or potasslumpassage over an ion exchange resin.

The saturated anhydrides used can be, for example, The compoundsaccording to the invention are solusuccinic anhydride, acetoxy succinicanhydride, methble in alkaline medium. They precipitate for the mostylsuccinic anhydride, diacetyl tartaric anhydride or dipart between pH 4and pH 6; some of them are soluble glycolic anhydride. The unsaturatedanhydrides used in an excess of acid.

The compounds according to the invention consti tute polyampholyteswhich present particularly advantageous properties in regard tofilmogens and sequestrants of heavy metal ions.

Actually, the compounds of the invention present a particularly markedsequestering action with regard to ions of heavy metals, such as ironand copper, and in particularly slight concentrations. These ions, whichgenerally come from water intake pipes, are particularly bothersome incertain industrial sections because they give rise to the formation ofprecipitates and they accelerate oxidation reactions. Thus, theirelimination is particularly desirable.

Further, the compounds according to the invention remain in solution inthe presence of alkaline earth ions, which advantageously differentiatesthem from natural polymers, such as alginates, which precipitate in anaqueous solution in the presence of these ions.

The combination of these two properties permits the compounds of thepresent invention to find a particularly interesting application assequestrants of' heavy metal ions in the food, pharmaceutical andtextile industries. Their sequestering property in the presence ofalkaline earth ions also makes it possible to use them in detergentcompositions. Their ampholyte character makes it possible to associatethem indifferently with cationic, anionic and, of course, non-ionicdetergents. In these applications, they present, in relation to usualsequestrants such as EDTA, the advantage of being able to be used inclearly smaller proportions The compounds according to the inventionfurther have filmogen properties. Actually, they give, on evaporation oftheir aqueous solution, perfectly transparent films, which arerelatively hard and not sticky, and which can be plastic or brittle,depending on the particular compound selected. Further, the films arecapable of exchanging water vapor with the surrounding environmentwithout losing their film characteristics.

This property, joined to the characteristic, which most of the compoundsaccording to the invention present, of precipitating from their aqueoussolutions at a pH between pH 4 and pH 6 i.e., in the pH zone of theskin, has a very interesting application in cosmetic or pharmaceuticalpreparations intended to moisten the skin or give it naturalconstituents.

The present invention also relates to cosmetic compositions comprisingan aqueous solution of at least one of the compounds according to thepresent invention in amounts of 0.1 to 20 percent by weight andpreferably from 0.25 to 10 percent by weight.

The cosmetic compositions of this invention also contain, besides thenovel chitosan derivatives, thickening or agglutinating agents such ascarboxyvinyl 5 tives, perfumes and the like.

These cosmetic compositions can be in the form of creams, lotions, gels,as well as in'the form of oils or aerosols.

The novel chitosan derivatives of this invention can be used in thepreparation of bath products and deodorants.

The following examples are given to illustrate the present invention.

EXAMPLE A Preparation of the product of condensation of chitosan withmaleic anhydride (compound No. 10)

To 20 g of chitosan, having a viscosity of 3.5 gps (96 milliequivalentsin amine groups), dispersed in 200 ml of water, there are added 8 ml ofconcentrated hydrochloric acid to neutralize exactly the free aminefunc-' tions, with stirring to complete dissolving. If necessary,

the undissolved chitosan particles can be filtered therefrom.

Then there are added at room temperature, alternately and in four equalfractions, on the one hand, 164

g (192 meq) of a sodium bicarbonate solution at 1.16

meq/g, and, on the other hand, 9.4 g (96 millimoles) of maleic anhydridepowder. Addition of each fraction takes 5 to 10 minutes, the interval ofintroduction between two fractions being 30 to 45 minutes.

When the reaction is completed, the acid number is measured and isdetermined to be 0.03 meq/g, which corresponds to a total acidity of12.5 meq.

The amount of base introduced is the stoichiometric amount necessary toneutralize both the hydrochloric acid used to make the chitosan salt andthe maleamic 4O acid formed.

The total acidity therefore takes into account the secondary reaction ofhydrolysis. The rate of reaction is (12.5 X 100/96) 13%, andconsequently the rate of condensation of maleic anhydride on chitosan is87 percent.

The compound thus prepared is isolated in acid form by adding 190 ml ofnormal hydrochloric acid. The resulting precipitate is filtered,drained, washed first with water and then with acetone, and dried.

The perfectly dry product can be ground and is in the form of a veryslightly tinted white powder.

Other compounds are prepared according to the same mode of operation.The starting products and reaction conditions are given in Table lbelow.

anhydride 1 20 3-4 50 TABLE lContinued Preci- Conc. Molar ReacpitaofCondenprotion tion Com- Polymer polysation por- Temp time 801- poundreactant mer reactant tions C. (hrs) vent No.

Chitosan itaconic ethyl (1 l7 cps) 2% anhydride 1 20 3-4 alcohol 60Chitosan succinic (3.5 cps) 5% anhydride 0.5 20 3-4 70 Chitosan succinicethyl (1 l7 cps) 2% anhydride 1 20 3-4 alcohol 90 Chitosan succinicwater (3.5 cps) 4.57r anhydride 1 25 8 (HCl) 70 bis Chitosan succinicwater (33 cps) 4.5% anhydride 0.5 25 8 (HCl) 80 Chitosan succinic water(33 cps) 3.5% anhydride 1 25 8 (HCl) 80 bis Chitosan citraconic (3.5cps) 4.5% anhydride 1.2 25 8 100 EXAMPLE B The compound thus obtained issoluble in an alkaline P f h f I 20 medium and an acid medium. It can bepreserved in fi g t e 9 0 i Q aqueous solution or isolated, byprecipitation, either in prepare m xamp e g ycoco l the form of sodiumsalt by addition of ethyl alcohol, or

There are dispersed 7 g of compound No. 10, or 20 at the isoelectricpoint by addition of hydrochloric meq, in 40 ml of water. Then 10 ml of2N soda are acid, in an aqueous or dilute alcohol medium. added toneutralize and solubilize it. To the solution 25 Other compounds, listedin Table 11 below, are prethus obtained there are added 1.5 g ofglycocoll (20 pared by the same mode of operation.

TABLE II Preci- Conc. Molar Reacpitaof protion tion Com- Polymer poly-Addition por- Tern time Solpound reactant mer reactant tions C. (hrs)vent No.

Ethanol- 10 12% amine 1.2 60 5 Ethanol 1 1 10 10% Glycocoll l 50 I 10 7%Cysteine 1 20 l Ethanol l3 Methio- 10 10% nine 1 60-90 10 14 Methyl 108% taurine 1 50-70 9 15 10% Ammonia 3 50 120 21 Methyl- 20 12% amine 32O 24 22 Dimethyl- 20 10% amine 1 20 20 23 Diethanol- 20 5% amine 1 6060 24 20 10% Glycocoll 1 60 21 25 Aspartic 20 15% acid 1 80 36 26 20 10%Cysteine 1 20 72 27 Ethylene- 40 8% diamine 0.14 90 3 Acetone 41 40 8%Sarcosine 10 24 I Ethanol 42 5% Serine 1.5 60 20 Ethanol 43 40 5%Cysteine 1 5 44 Glutamic Water 10 18% acid 1 -60 10 (HCl) 16 AsparticWater 10 10% acid I 25 10 (HCl) 17 Ethanol 10 12% Leucine 1 25 24Ethanol 18 10 4% Tyrosine 1 80-8 5 5 l9 Trypto- 10 10% phane 1 25Ethanol 11 A Gluta- 10 4.5% thion 1.2 25 24 Ethanol 12 A Penicill- 10 5%amine 1.1 25 72 Ethanol 13 A For condensation, only one acidity of thetwo of the Glutathion is neutralized. "The Pcnicillamine is solubilizedin acid form in water and is reacted in this form.

meq) dissolved in 10 m1 of 2N soda. The reaction mix- The followingexamples illustrate embodiments of ture is then heated at 50C for 1hour, under a nitrogen cosmetic compositions containing the compounds ofatmosphere. the present invention.

EXAMPLE 1 A softening cleansing milk is prepared having the followingcomposition in percent by weight:

Polyoxyethylene stcarate Glycerin monostearate (Arlacel 165) Vaselineoil Self emulsifiable PurCellin oil Lanolin Carboxyvinyi polymers(Carbopol 941 Triethanolamine Compound No. 70 bis Rose waterPreservative [methyl phydroxybenzoate) Perfume Demineralized water,sufficient for The fatty components (polyoxyethylene stearate, glycerinmonostearate, Vaseline oil, Pur Cellin oil and lanolin) are melted. Thismixture is then added to a so lution of Carbopol 941 obtained bydissolving the Carbopol in one part of water and then neutralizing itwith triethanolamine. An emulsion of the above components is then formedby stirring well.

Compound No. 70 bis is carefully dispersed in the rest of the water andneutralized by triethanolamine. Then the rose water, in which thepreservative is dissolved, is added.

Finally, the preceding emulsion is diluted with the so lution obtainedwith compound No. 70 his and the whole is perfumed.

When applied to the skin, this milk gives an impression of freshness andsoftness.

EXAMPLE 2 A hydrating and protective cleansing base is preparedaccording to the same mode of operation as for the milk of Example 1,said base having the following composition in percent by weight:

Stearic acid 2.0 2,6,l0,l5,l9,23-hexamethyltctracosane(perhydrosqualene) C H 20.0 Glycerin monostearate (Arlacel l65) 2.0Triethanolamine l.O Methyl parahydroxybenzoate 0.3 Carboxyvinyl polymers(Carbopol 94H 03 Triethanolamine 0.3 Compound No. 70 bis Perfume 0.3Demineralized water, sufficient for 100% This base has a good spreadingpower and assures a good protection to the skin.

EXAMPLE 3 According to the same mode of operation as for the milk ofExample 1, there is prepared a softening cream for legs that haveundergone depilation, said cream having the composition by weight inpercent of:

Fatty acid ester (Put Cellin oil) 2.0 Vaseline oil 70 Isopropylmyristate 1.5

2.6,10,15,I9,23-hcxamethyltetracosane (perhydrosqualene) C l-l LanolinAlcohols (Amerchol L lOl) Stearic acid Glycerin monostearate Hexadecylicalcohol Pure cetyl alcohol Preservative (methyl-p-hydroxybenzoate)Carboxyvinyl polymers (Carbopol 941) Tricthanolamine PerfumeTriethanolamine Compound No. 10

Demineralized water, sufficient for When applied to the skin, this creamgives'it an impression of softness.

EXAMPLE 4 According to the same mode of operation as for the milk ofExample 1, a hand cream is prepared with the composition in percent byweight:

Paraffin oil 200 Stearic acid 6.0 Triethanolamine 3.0 Glycerolmonostearate 2.0 Soybean lecithin [.0 Compound No. 10 3.0 Perfume 0.2Preservative( methyl-p-hydroxybenzoate) 0.3 Water. sufficient for l007rThis cream is very penetrating and imparts good suppleness to the skinshortly after its application thereto.

EXAMPLE 5 Preparation of an after-shave gel This gel having thefollowing composition in percent by weight:

Compound Not Carbopol 934 Triethanolamine Propylene glycol Preservative(methyl-p-hydroxybenzoate) Perfume Water sufficient for l is prepared asfollows:

A solution of compound No. 80 obtained by dispersing said compound inone part of water and neutralized with triethanolamine is mixed withCarbopol 934 neutralized with triethanolamine in propylene glycol. Thepreservative dissolved in water is then added to the whole. Perfume isthen added to the resulting mixture.

This gel, when applied to the skin, gives it a feeling of freshness.

EXAMPLE 6 Preparation of a body cream with the composition in percent byweight Vaseline oil Oleyl alcohol Glycerol monostearate Stearic acidCarboxyvinyl polymers (Carbopol 941) Triethanolamine Propylene glycolPreservative Compound No. 10

Dcmineralized water. sufficient for EXAMPLE 7 Preparation of a hydratinglotion This lotion having the following composition in percent byweight:

Hamamelis water 5 Compound No. 80

Aminomethylpropanol Preservative (methyl-p-hydroxybenzoate) PerfumeWater. sufficient for l is prepared as follows:

The preservative is dissolved in water. Compound No. 80 is dispersed inone part of water and aminomethylpropanol is dissolved in the remainingwater. The resulting three solutions are mixed and neutralized withaminomethylpropanol. The hamaelis water and perfume are then added. Thislotion, when applied to the skin, gives it a feeling of freshness.

. EXAMPLE 8 Preparation of a protective beauty cream Composition in 7rby weight:

Paraffin oil Stearic acid Triethanolamine Cetyl alcohol Compound No.

Perfume Preservative (methyl-p-hydroxybenzoate) Water, sufficient for 1EXAMPLE 9 A perfumed bath oil of the composition in percent by weight isprepared:

Propylene glycol lsopropyl myristate Compound No. 70 bis PerfumePreservative (methyl-p-hydroxybenzoate) Water. sufficient for 1 CompoundNo. 70 bis is dissolved in water, after neutralization withaminomethylpropanol, then the other ingredients of the formula areadded.

EXAMPLE 10 A bath cream of the composition in percent by weight isprepared:

Paraffin oil 40.0 Cetyl stearyl alcohol 3.0 Sorhitan monostearate 3.0Polyoxyethylene sorbitan monolaurate 4.0 Compound No. 70 bis 4.0 Perfume0.2 Preservative (methylp-hydroxybenzoate) 0.

Water. sufficient for 10071 The novel chitosan derivatives can alsoenter into the composition of filmogeneous products such as preparationsfor coloring the skin, deodorizing products and antispot products.

As examples there can be cited:

EXAMPLE 11 A filmogeneous product of the composition in percent byweight is prepared:

Compound No. 70 bis Triethanolamine or base amino acids.

sufficient amount for p Propylene glycol Titanium dioxide PigmentsCarboxymethyl cysteine Hexachlorophene Propyl-p-hydroxybenzoate Steriledemincralized water. sufficient for 10071 This product is used in skincare.

EXAMPLE 12 Preparation of deodorants for private hygiene in the form ofan aerosol foam Compound No. 10 3 Triethanolamine or base amino acids.

-Continued sufficient for pH 7 Lauryl sulfate 30 Lanolin 2Hypoallergenic perfume 0.2 Sterile water, sufficient for 100% To 90parts of the above mixture there are used 10 parts of the followingaerosol propellant in a 50/50 mixture: Freon, 114 (CClF CC1z)/Freonl2(CCl F EXAMPLE 13 Protective lotion The following composition isprepared in percent by weight:

Compound No. bis 0.5 Triethanolamine or base amino acids.

sufficient for pH 7 Propylene glycol 30 Sterile water. sufficient for10071 EXAMPLE 14 According to the method for preparing the milk ofExample 1, a protective day cream having the composition in percent byweight is prepared:

Stearic acid 2.00 Cosbiol 20.00 Glycerol monostearate 2.00Triethanolamine 1.00 Preservative (methyl-p-hydroxybenzoate) 0.30Carbopol 941 0.30 Compound 11 A 1.00 Perfume 0.30 Demineralized water.sufficient for 10071 This cream assures a good protection of the skin.

EXAMPLE 15 An after-shave fluid having the'composition in pering saidcompound in one part of water and then neutralizing it withtriethanolamine, is mixed with the propylene glycol. The preservative,dissolved in water, and then the perfume are added. This gel, whenapplied to the skin, gives the feeling of freshness.

EXAMPLE 16 A protective cream having the following composition inpercent by weight is prepared:

Paraffin oil 15.0 Stearic acid 5.0 Triethanolamine 2.5 Cetyl alcohol 3.0Compound No. 18 2.0 Perfume 0.2 Preservative (methyl-p-hydroxybenzoate)0.3 Water. sufficient for 10071 EXAMPLE 17 EXAMPLE 21 A bath producthaving the following composition in According to the method of preparingthe milk of Expercent by weight is prepared as follows: ample 1, acleansing base having the following composition in percent by weight isprepared:

Propylene glycol 8.0 lsopropyl myristutc 1.0 Compound No. 13 neutralizedwith 22355 323 g f y P p Glycerol monostearate er ume Preservative(methyl-p hydroxybenzoate) 0.3 Ohol Water. sufficient for 100%Triethanolamine 1:30 Prcservative (mcthyl-p-hydroxybenzoate) 0.30Compound No. 13 is dissolved in water after neutralgiiggffl gfl 16 3'38ization with aminomethylpropanol. Then the other Perfume 030 abovecomponents are added thereto Demineralized water. sufficient for 100%EXAMPLE 18 In the above cosmetic compositions the following A bath creamhaving the f ll i g composition in components employed are moreprecisely identified as percent by weight is prepared as follows:follows:

20 Amerchol L 101 -L1quid. multi-sterol. non-ionic,

surface-active penetrant, emollient and emulsifier. fi raffin oiflf l40.00 Sterols and higher alcohols are present only in their 0 Ohms andfree forms. Anhydrous, oil soluble, water dispers- C (Lanette 0) 3.00Sorbitun monostearate (Arlacel 60) 3,00 ible, practically odorless,tasteless and pale straw Sorbitan monolaurate (Tween 20) 4.00 ColorCompound No. 42 4.00 P f O2 Cosblol Perhydrosqualene. Preservative(methyl-p-hydroxybenzoate) 0.3 Carbopol 934 Carboxypolymethylene. waterbufficem for I007 Carbopol 941 a carboxyvinyl polymer Pur Cellin Oilfatt acid ester wiith alk lated rami- The fatty components are melted at75C. Compound fications y y No. 42 is dissolved in water with thepreservative and What is claimed o the resulting Soluuon heated to 75The l. Chitosan derivative consisting of randomly distribmeltedcomponents and solut on of compound l2 are med patterns of the formulae.mixed with stirring. After cooling, the perfume is incorporated. A

EXAMPLE 19 According to the same method for preparing the milk ofExample 1, a regenerating night cream having the following compositionin percent by weight is prepared:

Cetyl ether polyoxyethylene (10 moles) (BRLI 56) 2.00 Stearyl etherpolyoxyethylene l0 moles) (BRlJ 76) 2.00 4 Glycerin monostearute 4.00Perhydrosqualen (Cosbiol) 9.00 (B) Vaseline oil 32.00 CH OH Stcaric acid2.00 Compound 70 his 5.00 Perfume 0.30 and Preservative(methyl-p-hydroxybenzoate) 0.30 Triethanolamine 0.10 Dcmineralizedwater, sufficient for 100% EXAMPLE 20 A regenerating lotion having thefollowing composition in percent by weight is prepared as follows:

Compound No. l2 A 2.00 Rose water 50.00 Preservative(methyl-p-hydroxybenzoate) 0.3 Perfume 0.2 Sterile dcmineralized water,sufficient for 100% H liH The preservative is dissolved 1n water, thencompound No. 12 A is also dissolved. The rose water and co perfume areintroduced therein and the whole is fill tered and dyed. 3-30011 theproportions of these three patterns being, respectively, to 30 percentfor A, 5 to 40 percent for B and 30 to 90 percent for C, R representinga member selected from the group consisting of R 1T4 C C-HandR -=C-(O)-CH wherein R represents a member selected from the group consisting ofhydrogen and methyl, n is equal to (a) O, in which case R R and R eachindependently, represent a member selected from the group consisting ofhydrogen; methyl; hydroxy; acetoxy; amino; monoalkylamino ordialkylamino, wherein the alkyl moiety of each has 1 to 12 carbon atomsand wherein each is optionally interrupted by one or more nitrogen atomsor substituted by one or more amino, hydroxyl, mer-.

capto, carboxyl, alkylthio wherein the alkyl moiety has I to 8 carbonatoms and sulfonic groups; alkylthio wherein the alkyl moiety has 1 to 4carbon atoms and carries an amino residue; and a residue of glutathion,at least one of R R and R being hydrogen and radicals R and R being ableto form together a methylene radical, and (b) l, in which case R R and Reach represent hydrogen; and the salts formed by this derivative with abase selected from the group consisting of sodium hydroxide, potassiumhydroxide, ammonia, lime, magnesia and alkanolamine and an acid selectedfrom the group consisting of hydrochloric, phosphoric, acetic, lactic,tartaric and citric.

2. The process of preparing the chitosan derivative of claim 1,consisting essentially of acylating in an aque ous solution a chitosansalt of hydrochloric or acetic acid, said chitosan consistingessentially of 70 to 95 percent patterns B and 5 to 30 percent patternsA, said aqueous solution of the chitosan salt having a concentration of1 to 20 percent by weight of said salt, in the presence of a baseselected from the group consisting of sodium hydroxide, potassiumhydroxide and acid or neutral carbonates of sodium or potassium with asaturated or or unsaturated anhydride of the formula where R has themeaning given in claim 1 and n is equal to (a) O, in which case R R';,and R, each independently represent a member selected from the groupconsisting of hydrogen, methyl, hydroxy and acetoxy, at least one ofthese radicals being hydrogen and radicals R and R';, further being ableto form together methylene, and (b) 1, in which case R' R' and R, eachrepresent hydrogen, at a temperature between 10 and 50C.

3. Process according to claim 2, which includes adding to said aqueoussolution of said chitosan salt, alternately and by fractions, said basein dilute aqueous solution and said saturated or unsaturated anhydrideof formula Ill or IV as a powder or in solution in an inert solventselected from the group consisting of dioxane, tetrahydrofuran and ethylacetate.

4. Process according to claim 2 wherein the base is selected from thegroup consisting of sodium hydrox-.

6. Process according to claim 2 wherein the saturated anhydride isselected from the group consisting of succinic anhydride,acetoxysuccinic anhydride, methylsuccinic anhydride, diacetyltartaricanhydride and diglycolic anhydride.

7. Process according to claim 5 wherein said unsaturated anhydride ispresent in amounts of l to 2 moles.

of anhydride per equivalent of amine present in the molecule ofchitosan.

8. Process according to claim 6 wherein said saturated anhydride ispresent in amounts of 0.3 to 2 moles of anhydride per equivalent ofamine present in the molecule of chitosan.

9. Process according to claim 2 wherein said reaction is performed at atemperature between 15 and 30C.

10. Process according to claim 2, wherein the product resulting fromacylation of chitosan with an unsaturated anhydride is reacted with anamine selected from the group consisting of ammonia, methylamine,ethylamine, propylamine, butylamine, hexylamine, octylamine,dimethylamine, diethylamine, ethylenediamine, hexamethylenediamine,diethylenetriamine, triethylentetramine, tetraethylenepentamine,methanolamine, isopropanolamine, diethanolamine, B-mercaptoethylamine,glycocoll, alanine, leucine, isoleucine, valine, as-

partic acid, glutamic acid, serine, lysine, cysteine, me-

thionine, cysteic acid, taurine, methyltaurine, penicillamine,glutathion, tryosine and tryptophane, at a temperature between 20 and60C for a period of 2 to hours.

11. Process according to claim 9 wherein said amine is present inamounts of 0.1 to 10 moles per unsaturated pattern present in thechitosan molecule after re- (III) action with unsaturated anhydride.

12. Process according to claim 10 wherein the reaction mixture is keptfor 4 hours at 50C.

13. Process according to claim 10 wherein said addition reaction isperformed under a nitrogen atmosphere.

14. Process according to claim 2, wherein the product of the acylationreaction is precipitated by adding an acid to the reaction mixture.

15. Process according to claim 2, wherein the product of acylationreaction is isolated by adding an organic solvent to the reactionmixture.

16. The process of claim 15 wherein said organic solvent is an alcoholor acetone.

1. CHITOSAN DERIVATIVE CONSISTING OF RANDOMLY DISTRIBUTED PATTERNS OFTHE FORMULAE:
 1. Chitosan derivative consisting of randomly distributedpatterns of the formulae:
 2. The process of preparing the chitosanderivative of claim 1, consisting essentially of acylating in an aqueoussolution a chitosan salt of hydrochloric or acetic acid, said chitosanconsisting essentially of 70 to 95 percent patterns B and 5 to 30percent patterns A, said aqueous solution of the chitosan salt having aconcentration of 1 to 20 percent by weight of said salt, in the presenceof a base selected from the group consisting of sodium hydroxide,potassium hydroxide and acid or neutral carbonates of sodium orpotassium with a saturated or or unsaturated anhydride of the formula 3.Process according to claim 2, which includes adding to said aqueoussolution of said chitosan salt, alternately and by fractions, said basein dilute aqueous solution and said saturated or unsaturated anhydrideof formula III or IV as a powder or in solution in an inert solventselected from the group consisting of dioxane, tetrahydrofuran and ethylacetate.
 4. Process according to claim 2 wherein the base is selectedfrom the group consisting of sodium hydroxide, potassium hydroxide,sodium acid carbonate and potassium acid carbonate.
 5. Process accordingto claim 2 wherein the unsatuated anhydride is selected from the groupconsisting of maleic anhydride, itaconic anhydride and citraconicanhydride.
 6. Process according to claim 2 wherein the saturatedanhydride is selected from the group consisting of succinic anhydride,acetoxysuccinic anhydride, methylsuccinic anhydride, diacetyltartaricanhydride and diglycolic anhydride.
 7. Process according to claim 5wherein said unsaturated anhydride is present in amounts of 1 to 2 molesof anhydride per equivalent of amine present in the molecule ofchitosan.
 8. Process according to claim 6 wherein said saturatedanhydride is present in amounts of 0.3 to 2 moles of anhydride perequivalent of amine present in the molecule of chitosan.
 9. Processaccording to claim 2 wherein said reaction is performed at a temperaturebetween 15* and 30*C.
 10. Process according to claim 2, wherein theproduct resulting from acylation of chitosan with an unsaturatedanhydride is reacted with an amine selected from the group consisting ofammonia, methylamine, ethylamine, propylamine, butylamine, hexylamine,octylamine, dimethylamine, diethylamine, ethylenediamine,hexamethylenediamine, diethylenetriamine, triethylentetramine,tetraethylenepentamine, methanolamine, isopropanolamine, diethanolamine,Beta -mercaptoethylamine, glycocoll, alanine, leucine, isoleucine,valine, aspartic acid, glutamIc acid, serine, lysine, cysteine,methionine, cysteic acid, taurine, methyltaurine, penicillamine,glutathion, tryosine and tryptophane, at a temperature between 20* and60*C for a period of 2 to 140 hours.
 11. Process according to claim 9wherein said amine is present in amounts of 0.1 to 10 moles perunsaturated pattern present in the chitosan molecule after reaction withunsaturated anhydride.
 12. Process according to claim 10 wherein thereaction mixture is kept for 4 hours at 50*C.
 13. Process according toclaim 10 wherein said addition reaction is performed under a nitrogenatmosphere.
 14. Process according to claim 2, wherein the product of theacylation reaction is precipitated by adding an acid to the reactionmixture.
 15. Process according to claim 2, wherein the product ofacylation reaction is isolated by adding an organic solvent to thereaction mixture.